Applications of NMR spectroscopy to systems biochemistry

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128 Scopus citations

Abstract

The past decades of advancements in NMR have made it a very powerful tool for metabolic research. Despite its limitations in sensitivity relative to mass spectrometric techniques, NMR has a number of unparalleled advantages for metabolic studies, most notably the rigor and versatility in structure elucidation, isotope-filtered selection of molecules, and analysis of positional isotopomer distributions in complex mixtures afforded by multinuclear and multidimensional experiments. In addition, NMR has the capacity for spatially selective in vivo imaging and dynamical analysis of metabolism in tissues of living organisms. In conjunction with the use of stable isotope tracers, NMR is a method of choice for exploring the dynamics and compartmentation of metabolic pathways and networks, for which our current understanding is grossly insufficient. In this review, we describe how various direct and isotope-edited 1D and 2D NMR methods can be employed to profile metabolites and their isotopomer distributions by stable isotope-resolved metabolomic (SIRM) analysis. We also highlight the importance of sample preparation methods including rapid cryoquenching, efficient extraction, and chemoselective derivatization to facilitate robust and reproducible NMR-based metabolomic analysis. We further illustrate how NMR has been applied in vitro, exvivo, or in vivo in various stable isotope tracer-based metabolic studies, to gain systematic and novel metabolic insights in different biological systems, including human subjects. The pathway and network knowledge generated from NMR-and MS-based tracing of isotopically enriched substrates will be invaluable for directing functional analysis of other omics data to achieve understanding of regulation of biochemical systems, as demonstrated in a case study. Future developments in NMR technologies and reagents to enhance both detection sensitivity and resolution should further empower NMR in systems biochemical research.

Original languageEnglish
Pages (from-to)18-53
Number of pages36
JournalProgress in Nuclear Magnetic Resonance Spectroscopy
Volume92-93
DOIs
StatePublished - Feb 1 2016

Bibliographical note

Funding Information:
This work was supported in part by United States National Institute of Health ( NIH ) grants: 1R01CA118434-01A2 , 1U24DK097215-01A1 , P01 CA163223-01A1 and NIH 5R01ES022191-04 . NIH had no role in the preparation of the article.

Publisher Copyright:
© 2016 Elsevier B.V. All rights reserved.

Keywords

  • Hyperpolarization
  • In vivo NMR
  • Metabolic network and flux
  • Stable isotope resolved metabolomics
  • Stable isotope tracers

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry
  • Nuclear and High Energy Physics
  • Spectroscopy

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